Amine salts of antimonic and phenyl stibonic acids and process of preparing the same



Patented Jan. 22, 1935 1,988,632

AMINE SALTS OF ANTmONl IC AND PHENYL S'I'IBONIO ACIDS AND PROCESS OF PRE- PARJNG THE SAME Hans Schmidt, Elberfeld-Vohwinkel, Germany, assignor to Winthrop Chemical Company, Inc., New York, N. Y., a corporation of New York No Drawing. Application April 5, 1929, Serial No. 352,898. In Germany February 24, 1927 30 Claims. (Cl. 260-11) The present invention relates to a process of valuable substances against infectious diseases, preparing stable, medicinally active amine salts especially for injections. of antimonic and 'phenyl stibonic acids with The following exampleswillillustratemyinvenamines and to the new substances obtainable tion, without limiting it thereto: thereby. Example 1.-Para-aminophenyl stibonic acid, 5 In accordance with the present invention, obtainable in the known manner by saponificapharmaceutically valuable substances are obtion of 150 grams of para-acetylaminophenyl tained by reacting upon an antimony acid or a stibonic acid, is shaken, while still moist with a stibonic acid, suchas aphenyl stibonic acid which twice normal aqueous solution of diethylamine.

may be represented by the formula: The diethylamine solution is gradually added until 10 solution is effected. The solution is filtered 0 and the diethylene-para-aminophenyl stibonate R ,5 formed is precipitated by pouring its solution into acetone; the precipitated product is filtered and OH dried in a desiccator. A pale colored powder is 15 obtained, dissolving in water, even after prolonged storing to give solution of the desired stability. on the addit on of caustic alkali solution to the solution, an odor of diethylamine can be observed. On the addition of diluted hydro- 0 chloric acid and an aqueous solution of hydrogensulfide to the strongly diluted solution, it becomes yellow; on heating, antimony sulfide is formed. The dry substance decomposes on heating without melting.

Example 2.-Para-aminophenyl stibonic acid obtainable as described in Example 1, while still moist, is shaken with water whereby piperazine is added until a clear solution is obtained. The new piperazine-para-aminophenyl stibonate is separated as described in Example 1.

Example 3.-Antimonic acid, obtainable in the customary manner from antimony pentachloride by introducing the same into water, filtering and washing, is dissolved by means of a quantity of 5-normal diethylamine, necessary to produce a upon each other may be vaned wltmn t widest neutral solution; the solution is filtered and evaplimitsi but generally less than eqmvalent of orated. The diethylamine antimonate remains the amine calculated on the stibomc or antimonic behind in the form or glassy crusts. which on' acid being sumcient due to the mghmolecular powdering yield a colorless powder, readily soi- 40 state, in which the acids of antimony generally uble in water. are P owing to complex state of the Example 4.-65 grams of freshly precipitated, mummy acids of antlmony are present in moist meta-chloro-para-acetylaminophenyl sticomplex state, a formula. of the products formed homo acid (:33 grams f the dry substance) are an i1119451011 of the Pmcess cammt' be givendissolved by means of 80 ccs. of methyl alcohol 45 But it may be stated that, of course, thq and the requisite quantity of twice normal dibetween the antim ny acids and the ammas ethylamine solution (about 25 ccs.). The soluta t a y appears as neutralization of the acid" tion is filtered and stirred into ether. Thereupon i y of the n i y acids by the amines- From the diethylan'iine-meta-'chloro-para-acetylarninotheir solutions, the new compounds are obtainable phenyl-stibonate i precipitated i a finely 1- 50 y p rating to dryness or. y adding a rganic vided state. After filtering and drying, a pale precipitant, such as ether or acetone. colored powder, readily soluble in water, is ob- The n w compounds are lly colorless tained. In a similar manner, there can be proyellowish colored powders, which are generally duced, for example, a diethylamine salt of disoluble in water and which are pharmaceutically (para-acetylaminodlphenyl) -stibonic acid. 55

wherein R stands for a phenyl radical which may be substituted for example by halogen, the amino-, substituted amino-, hydroxy-groups, or by react- 20 mg upon said acids of antimony in their higher molecular complex state (compare Schmidt, Annalen der Chemie, volume 421, page 174 following) with a primary, secondary or tertiary amine, such as methylamine, diethylamine, piperazine, qui- 2 nine and the like at room temperature or at most at the temperature of the water bath. The process is carried out by allowing the two components to interact upon each other either in aqueous solution or in a suitable organic solvent, such as 30 methvlalcohol or ethylalcohol; the most favorable method of carrying out the process consists in finely suspending the organic or inorganic antimony acid in water, and introducing in small portions an amine until the whole of the anti- 35 mony acid has dissolved. The quantities of the two components which may be allowed to react Example 5.Freshly precipitated, moist paraaminophenyl-stibonic acid is dissolved by grinding with an excess 0! ethylene dlamine and alter filtration the solution is precipitated by stirring into acetone. A pale colored powder-of ethylene diamine-para-aminophenyl stlbonate is obtained, readily soluble in water.

Example 6.10 grams of para-acetylaminophenyl-stibonic acid and 10 grams of quinine base-are dissolved by heating in 50 cos. of methylalcohol. The solution is filtered and the quininepara-acetylaminophenyl stibonate formed is precipitated by stirring into ether, filtered and washed with ether. The salt does not dissolve in water, but yields a neutral or nearly neutral suspension.

In a similar manner, there can be produced, for example, salts of other basic quinoline derivatives. A salt which is insoluble in water is also obtained when reacting, for instance, upon paraacetylaminophenyl stibonic acid with 1,2-dimethyl-3-dimethylamino-1-propyl para-aminobenzoate of the formula Example 7.Antimonic acid, obtainable from antimony pentachloride as described in Example 3, is dissolved on the water bath in a quantity of twice normal diethylaminoethanol solution, necessary for the production of a neutral solution; the solution is filtered and evaporated to dryness in vacuo. The diethylamino ethanol antimonate is obtained in the form of a colorless, somewhathygroscopic powder, readily soluble in water.

Example 8. grams of freshly precipitated, moist para-aminophenyl stibonic acid paste are shaken with some water and about 20 cos. of twice normal diethylaminoethanol solution until dissolved. The solution is filtered, treated with diethylaminoethanol until it gives a weakly alkaline reaction, and the resulting diethylaminoethanol-para-aminophenyl stibonate is precipitated by stirring the solution into acetone. After filtering and washing, it is dried in a desiccator. It is a pale colored powder, readily soluble in water.

Example 9.100 grams of freshly precipitated,

moist para-aminophenyl-stibonic acid paste are After drying a pale colored powder is obtained,.

which yields in water a suspension having a neutral reaction.

This application is a continuation-impart of my Ser. No. 254,900, filed February 16, 1928.

I claim:-

1. The process which comprises suspending an antimonic acid of the group consisting of antimonic and phenyl-stibonic acids in water and slowly introducing an amine while stirring until a clear solution has formed.

2. The process which comprises suspending a phenyl-stibonic acid which is substituted in the phenyl nucleus by halogen, amino-, acylaminoor hydroxyl groups in water and slowly introducing an amine while stirring until a clear solution has formed.

3. The process which comprises suspending an amino-phenyl-stibonic acid in water and slowly introducinganaminewhilestirringuntilaclear solution has formed.

4. The process which comprises suspending para-amlno-phenyl-stibonic acid in water and slowly introducing an amine while stirring until a clear solution has formed.

5. The process which comprises suspending an antimonic acid of the group consisting of antimonic and phenyl-stibonic acids in water and slowly introducing diethylamine while stirring until a clear solution has formed.

6. The process which comprises suspending a phenyl-stibonic acid which is substituted in the phenyl nucleus by halogen, amino-, acylaminoor hydroxyl groups, in water and slowly introducing diethylamine while stirring until a clear solution has formed.

'1. The process which comprises suspending para-aminophenyl-stibonic acid in water and slowly introducing diethylamine while stirring until a clear solution has formed.

8. A salt of an antimonic acid of the group consisting of antimonic acids and phenyl stibonic acids, with an amine, being generally a colorless to yellowish powder, being generally soluble in water and being a pharmaceutically valuable substance against infectious diseases.

9. A salt of a phenyl-stibonic acid which is substituted in the phenyl nucleus by halogen, amino-, acylaminoor hydroxyl groups, withan amine. being generally a colorless to yellowish powder, being generally soluble in water and being apharmaceutically valuable substance against infectious diseases. 1

10. A salt of para-amino-phenyl-stibonic acid with an amine, being generally a colorless to yellowish powder, being generally soluble in water and being a pharmaceutically valuable substance against infectious diseases.

11. A salt of an antimonic acid'ot the group consisting of antimonic acids and phenyl stibonic acids, with dietbylamine, being generally a colorless to yellowish powder, being generally soluble in water and being a pharmaceutically valuable substance against infectious diseases.

12. Asalt of a phenyl-stibonic acidwhich is substituted in the phenyl nucleus, by halogen, am-

ino-, acylaminoor hydroxyl groups, with di-' ate, being a pale colored powder, soluble in water and being a pharmaceutically valuable substance against infectious diseases.

14. The process which comprises reacting upon an antimonic acid of the group consisting of antimonic acids and phenyl stibonic acids with an amine.

15. The process which comprises reacting upon a phenyl-stibonic acid which is substituted in the benzene nucleus by halogen, amino acylaminoor hydroxyl groups with an amine.

16. The process which comprises reacting upon an amino-phenyl-stibonic acid with an amine.

17. The process which comprises reacting upon para-amino-phenyl-stibonic acid with an amine.

1-8. The process which comprises reacting upon a phenyl-stibonic acid with a secondary amine.

19. The process which comprises reacting upon a phenyl-stibonic acid which is substituted in the benzene nucleus by halogen, amino-, acylaminoor hydroxyl groups, with a secondary amine.

20. The process which comprises reacting upon an amino-phenyl-stibonic acid with a secondary amine.

21. The process which comprises reacting upon para-amino-phenyl-stibonic acid with a secondary amine.

22. The process which comprises reacting upon an antimonic acid of the group consisting of antimonic acids and phenyl-stibonic acids with an amine in a solvent of the group consisting of water, methylalcohol and ethylalcohol.

23. The process which comprises reacting upon a. phenyl-stibonic acid which is substituted in the benzene nucleus by halogen, amino-, acylaminoor hydroxyl groups, with an amine in a solvent of the group consisting of water, methylalcohol and ethylalcohol.

24. The process which comprises reacting upon an amino-phenyl-stibonic acid with an amine in a solvent of the group consisting of water, methylalcohol and ethylalcohol.

25. The process which comprises reacting upon para-amino-phenyl-stibonic acid with an amine in a solvent of the group consisting of water, methylalcohol and ethylalcohol.

26. The process which comprises reacting upon a. phenyl-stibonic acid with a secondary amine in a solvent of the group consisting of water, methylalcohol and ethylalcohol.

2'1. The process which comprises reacting upon a phenyl-stibonic acid which is substituted in the benzene nucleus by halogen, amino-, acylaminoor hydroxyl groups, with a secondary amine in a solvent of the group consisting of water, methylalcohol and ethylalcohol.

28. The process which comprises reacting upon an amino-phenyl-stibonic acid with a secondary amine in a solvent of the group consisting of water, methylalcohol and ethylalcohol.

29. The process which comprises reacting upon para-amino-phenyl-stibonic acid with a secondary. amine in a solvent of the group consisting of water, methylalcohol and ethylalcohol.

30. Diethylaminoethanol antimonate, being a colorless, somewhat hygroscopic powder, readily soluble in water and being a pharmaceutically valuble substance against infectious diseases.

HANS SCHMIDT. [L.s.1

CERTIFICATE OF CORRECTION. Patent No. 1,988,552. January 955- HANS scmum.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction -as follows: Page 1, first column, lines 5 and strike out the Words "with amines lines 1;} and 141 strike out "of antimony are present in s. complex state"; and second column, line 12, for "diethylene" read diethylamine-; line 55, for "acetylami nodiphenyl" read --acety1aminophenyl--; and that the said Letters Patent should be read with this correction therein that the same may conform to the record of the case in' the Patent Office. 7 I

Signed and sealed this 25th day of September, A. D. 1915.

Leslie Frazer (Seal) First Asistant Commissioner of Patents. 

